Do Sleep and Circadian Rhythm Disturbances Impact the Cognitive and Behavioural Development of Children With Autism?

Not Applicable

• Conditions: Autism Spectrum Disorder

• Registration Number: NCT02878499
• Lead Sponsor: University Hospital, Strasbourg, France

Brief Summary

The primary objective of this study is to undertake a longitudinal investigation of the impact of sleep and circadian rhythm disturbances on cognitive and behavioural trajectories in children with autism spectrum disorder (ASD) age 3-10 years old.

This innovative study will use objective quantifiable measures of sleep and circadian rhythms in addition to subjective measures.

The investigators aim to assess the hypotheses that, in pre-pubertal children with ASD,

1. sleep disturbances are correlated with circadian rhythm disturbances;

2. both sleep and circadian rhythm disturbances are negatively correlated with cognitive performance and positively correlated with behavioural disturbances;

3. sleep and circadian rhythm disturbances, most notably abnormal melatonin secretion, impact the cognitive and behavioural development of children with ASD, depending on age (prospective longitudinal analyses).

Detailed Description

Not available

Study Timeline

• Study Start: 2012-12-19
• Study First Submitted: 2016-06-14
• Study First Submitted QC: 2016-08-19
• Study First Posted: 2016-08-25
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-28
• Last Update Posted: 2022-06-30
• Primary Completion: 2022-12
• Study Completion: 2023-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 105

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Change in nocturnal melatonin secretion at 1 year follow-up and 2 year follow-up compared to baseline	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up	Nocturnal melatonin secretion (6-SMT measured in night urine from 8pm to 8am)
Change in aberrant Behaviour Checklist (ABCL) global score at 1 year follow-up and 2 year follow-up compared to baseline	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Change in sleep latency at 1 year follow-up and 2 year follow-up compared to baseline	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up	Sleep latency derived from actigraphy
Change in sleep fragmentation index at 1 year follow-up and 2 year follow-up compared to baseline	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up	Sleep fragmentation index derived from polysomnography (PSG)
Change in amplitude of the day-night melatonin secretion at 1 year follow-up and 2 year follow-up compared to baseline	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up	Amplitude of the day-night melatonin secretion (6 sulfatoxy-melatonin (6-SMT) measured in 12h-night versus 12h-day urine)
Change in non-verbal index (INV, derived from the Kaufmann-Assessment Battery fir Children II (K-ABC II)) at 1 year follow-up and 2 year follow-up compared to baseline	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Change in Raven performance IQ at 1 year follow-up and 2 year follow-up compared to baseline	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up	Raven performance IQ derived from Raven progressive matrices (CPM-BF) at 1 year follow-up and 2 year follow-up compared to baseline
Change in Autism Diagnostic Observation Schedule (ADOS), module 1-3: part 'D' et 'E' (repetitive and abnormal behaviour) at 1 year follow-up and 2 year follow-up compared to baseline	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Change in verbal intelligence quotient (IQ) at 1 year follow-up and 2 year follow-up compared to baseline	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up	Change in verbal intelligence quotient (IQ) derived from the appropriate Wechsler scales for children (WPPSI or WISC) at 1 year follow-up and 2 year follow-up compared to baseline

Secondary Outcome Measures

Name	Time	Method
Sleep spindle density in light slow wave sleep	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Spectral analysis of the sleep electro-encephalogram (EEG)	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Level of ferritin in plasma	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
presence of an intrinsic sleep disorders (e.g. obstructive or central sleep apnea syndrome, restless legs syndrome and periodic limb movements during sleep…)	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Total sleep time (TST)	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Time and percentage of TST spent in different sleep stages (slow wave sleep, rapid eye movement (REM) sleep)	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
24h urinary 6-sulfatoxymelatonin levels (ng/ml)	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Density of rapid eye movements in REM sleep	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Inter-daily stability (IS) and intra-daily variability (IV) of circadian rhythms (actigraphy derived)	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up	Level of ferritin in plasma
Circadian phase of body temperature	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up

Trial Locations

Locations (5)

CHRU de Lille - Hôpital Roger Salengro; 🇫🇷 Lille, France

CHU de Lyon - CHS Le Vinatier; 🇫🇷 Lyon, France

CHU Gui de Chaulhiac; 🇫🇷 Montpellier, France

Hôpitaux Universitaires de Strasbourg; 🇫🇷 Strasbourg, France

CHU de TOURS - Hôpital Bretonneau; 🇫🇷 Tours, France